The factors which ultimately determine calcium and phosphate excretion are not well-defined. Previously work by the applicant suggests that the distal nephron is a critical factor in the regulation of urinary excretion of these ions. The specific aim of this research proposal is to apply the techniques of micropuncture to evaluate the role of the terminal nephron in pathophysiologic states of renal calcium and phosphate transport. Chronic phosphate depletion in dogs (an example of hypercalciuria in man and various experimental animals), and familial hypophosphatemic rickets in man and mouse (an example of an important disorder of renal phosphate reabsorption) will serve as experimental models in these studies. They will provide a clinically relevant setting in which to test the hypothesis of the central role of the distal nephron in regulation divalent ion excretion and thereby allow a fuller understanding of the pathophysiologic mechanisms of hypercalciuric and hyperphosphaturic states.